BEMESETRON

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H17Cl2NO2
Molecular Weight	314.207
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1[C@H]2CC[C@@H]1C[C@@H](C2)OC(=O)C3=CC(Cl)=CC(Cl)=C3

InChI

InChIKey=MNJNPLVXBISNSX-WDNDVIMCSA-N

InChI=1S/C15H17Cl2NO2/c1-18-12-2-3-13(18)8-14(7-12)20-15(19)9-4-10(16)6-11(17)5-9/h4-6,12-14H,2-3,7-8H2,1H3/t12-,13+,14+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8452114 | https://www.ncbi.nlm.nih.gov/pubmed/17948891

Bemesetron, also known as MDL 72222, is a potent and highly selective antagonist of neuronal 5-hydroxytryptamine receptors, 5HT3. Bemesetron possesses antiemetic efficacy in comparison with a high-dose metoclopramide regimen (HDM) for chemotherapy-induced nausea and vomiting. But this application is not clinically used. Drug is used as scientific tool for the study 5HT3 receptor properties in the actions of drugs of abuse.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 3 (5-HT3) receptor 59 Target ID: CHEMBL2094132 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3114804	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Nausea and vomiting 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8452114	Palliative		Not Provided 504	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Effects of 5-HT2 and 5-HT3 receptors on the modulation of nociceptive transmission in rat spinal cord according to the formalin test.	2001 Jul 13	11470259
Serotonin and NO complementarily regulate generation of oscillatory activity in the olfactory CNS of a terrestrial mollusk.	2001 Jun	11387408
Pharmacology of serotonin receptors modulating electrically-induced [3h]-norepinephrine release from isolated mammalian iris-ciliary bodies.	2002 Aug	12222764
Dual cooperative allosteric modulation of binding to ionotropic glycine receptors.	2002 Dec	12504915
5-HT3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not methylphenidate-induced neurochemical and behavioral effects in the rat.	2002 Feb	11823886
5-HT2 and 3 receptor antagonists suppress the response of rat type I slowly adapting mechanoreceptor: an in vitro study.	2003 Apr 18	12676383
Conditional involvement of striatal serotonin3 receptors in the control of in vivo dopamine outflow in the rat striatum.	2003 Feb	12603267
Pretreatment with serotonin 5-HT(3) receptor antagonists produces no observable blockade of long-term motor sensitization to cocaine in rats.	2003 Feb	12451437
Effects of ginsenoside Rg2 on the 5-HT3A receptor-mediated ion current in Xenopus oocytes.	2003 Feb 28	12661769
Roles for CCK1 and 5-HT3 receptors in the effects of CCK on presympathetic vasomotor neuronal discharge in the rat.	2003 May	12770947
Reduced 5-HT3 receptor binding and lower baseline plus maze anxiety in the alcohol-preferring inbred fawn-hooded rat.	2004 Feb	14751456
5HT2 and 5HT3 receptors' contribution to modeling of post-serotonin respiratory pattern in cats.	2004 Sep 24	15350826
Antinociceptive effect of shakuyakukanzoto, a Kampo medicine, in diabetic mice.	2005 Dec	16314688
Blockade of 5-HT(3) receptor with MDL7222 and Y25130 reduces hydrogen peroxide-induced neurotoxicity in cultured rat cortical cells.	2005 Dec 5	16112139
Effects of quipazine and m-chlorophenylbiguanide (m-CPBG) on the discrimination of durations: evidence for the involvement of 5-HT2A but not 5-HT3 receptors.	2005 Feb	15706137
Evaluation of the anti-emetic potential of anti-migraine drugs to prevent resiniferatoxin-induced emesis in Suncus murinus (house musk shrew).	2005 Jan 31	15680276
The serotonin type 3A receptor facilitates luteinizing hormone release and LHbeta promoter activity in immortalized pituitary gonadotropes.	2005 Jun	16077169
Mechanisms of analgesic action of neurotropin on chronic pain in adjuvant-induced arthritic rat: roles of descending noradrenergic and serotonergic systems.	2005 Mar	15764839
Effects of quipazine and m-chlorophenylbiguanide (m-CPBG) on temporal differentiation: evidence for the involvement of 5-HT2A but not 5-HT3 receptors in interval timing behaviour.	2005 Sep	15864559
Blockade of 5-HT(3) receptor with MDL 72222 and Y 25130 reduces beta-amyloid protein (25--35)-induced neurotoxicity in cultured rat cortical neurons.	2005 Sep 27	16150439
Rewarding properties of 1-benzylpiperazine, a new drug of abuse, in rats.	2006 Apr	16623856
Effects of repeated daily treatments with a 5-HT3 receptor antagonist on dopamine neurotransmission and functional activity of 5-HT3 receptors within the nucleus accumbens of Wistar rats.	2006 Jun	16828150
Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice.	2006 May	16288851
Involvement of 5-HT receptors in the development and expression of methamphetamine-induced behavioral sensitization: 5-HT receptor channel and binding study.	2006 Nov	16942594
A dual role of 5-hydroxytryptamine receptor 3 in serotonin induced ion transport in rat distal colon.	2008 Apr 14	18313044
Dopamine neurotransmission is involved in the attenuating effects of 5-HT3 receptor antagonist MDL 72222 on acute methamphetamine-induced locomotor hyperactivity in mice.	2008 Jan	17948891
Long-term depression in the superior cervical ganglion of the rat.	2008 Oct 9	18718451
Effects of triterpenoids from Poria cocos Wolf on the serotonin type 3A receptor-mediated ion current in Xenopus oocytes.	2009 Aug 1	19446542
Mechanisms of analgesic action of pulsed radiofrequency on adjuvant-induced pain in the rat: roles of descending adrenergic and serotonergic systems.	2009 Mar	18539061
Effects of serotonin on acid secretion in isolated rat stomach: the role of 5-HT3 receptors.	2009 Nov 30	20359130
GABA(A) receptors mediate the attenuating effects of a 5-HT(3) receptor antagonist on methamphetamine-induced behavioral sensitization in mice.	2010 Apr	19953653
The chemical basis of pharmacology.	2010 Dec 7	21058655
5-HT3 receptor-dependent modulation of respiratory burst frequency, regularity, and episodicity in isolated adult turtle brainstems.	2010 Jun 30	20399913

Patents

Sample Use Guides

In Vivo Use Guide

MDL 72,222 (Bemesetron) was given in 20 mg intravenous doses 30 minutes before chemotherapy, as well as 2, 6, and 12 hours after chemotherapy infusion

Route of Administration: Intravenous

In Vitro Use Guide

The properties of MDL 72222 (bemesetron) with potent and selective blocking actions at certain excitatory 5-hydroxytryptamine (5-HT) receptors on mammalian peripheral neurones, are described. On the rabbit isolated heart, MDL 72222 was a potent antagonist of responses mediated through the receptors for 5-HT present on the terminal sympathetic fibres. The threshold for antagonism was approximately 0.1 nM and the negative logarithm of the molar concentration of MDL 72222 which reduced the chronotropic response of the isolated rabbit heart to twice an ED50 of 5-HT to that of the ED50 was 9.27. MDL 72222 was also highly selective since responses to the nicotine receptor agonist, dimethylphenylpiperazinum iodine (DMPP), were inhibited only at concentrations more than 1000 times those necessary to inhibit 5-HT.

Name

Type

Language

BEMESETRON

Official Name

English

MDL-72,222

Code

English

MDL 72,222

Code

English

1αH,5αH-Tropan-3α-yl 3,5-dichlorobenzoate

Common Name

English

BEMESETRON [USAN]

Common Name

English

8-METHYL-8-AZABICYCLO(3.2.1)OCTAN-3-YL 3,5-DICHLOROBENZOATE

Systematic Name

English

bemesetron [INN]

Common Name

English

3-Tropanyl-3,5-dichlorobenzoate

Common Name

English

MDL-72222

Code

English

BENZOIC ACID, 3,5-DICHLORO-, 8-METHYL-8-AZABICYCLO(3.2.1)OCT-3-YL ESTER, ENDO-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94726